Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapeutic Strategy for Acute Kidney Injury.

Jia-Kun Li,Zhe Luo,Cheng Yang,Dan-Lei Huang,Guo-Wei Tu,Ying Su,Ming-Hao Luo,Jing-Chao Luo

doi:10.3389/fimmu.2021.684496

Abstract

Acute kidney injury (AKI) is a common and potential life-threatening disease in patients admitted to hospital, affecting 10%–15% of all hospitalizations and around 50% of patients in the intensive care unit. Severe, recurrent, and uncontrolled AKI may progress to chronic kidney disease or end-stage renal disease. AKI thus requires more efficient, specific therapies, rather than just supportive therapy. Mesenchymal stem cells (MSCs) are considered to be promising cells for cellular therapy because of their ease of harvesting, low immunogenicity, and ability to expand in vitro. Recent research indicated that the main therapeutic effects of MSCs were mediated by MSC-derived extracellular vesicles (MSC-EVs). Furthermore, compared with MSCs, MSC-EVs have lower immunogenicity, easier storage, no tumorigenesis, and the potential to be artificially modified. We reviewed the therapeutic mechanism of MSCs and MSC-EVs in AKI, and considered recent research on how to improve the efficacy of MSC-EVs in AKI. We also summarized and analyzed the potential and limitations of EVs for the treatment of AKI to provide ideas for future clinical trials and the clinical application of MSC-EVs in AKI.

Highlights

Acute kidney injury (AKI) is a common and sometimes life-threatening disease in patients admitted to hospital, affecting 10%–15% of all hospitalizations and around 50% of patients in the intensive care unit [1]
We review the possible therapeutic mechanisms of Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) in AKI, and consider recent research aimed at improving the therapeutic efficacy of MSC-EVs in AKI
Recent studies showed that mRNAs for factors such as IL-10, IGF-1R, hepatocyte growth factor (HGF), DNA-directed RNA polymerases I, II, and III subunit RPABC1, and vascular endothelial growth factor (VEGF) could be loaded into EVs and transported to the target cells to exert translational effects, including anti-inflammation, anti-fibrosis, and anti-apoptosis effects, promoting proliferation, improving renal function, and reducing kidney injury [43, 71]

Summary

INTRODUCTION

Acute kidney injury (AKI) is a common and sometimes life-threatening disease in patients admitted to hospital, affecting 10%–15% of all hospitalizations and around 50% of patients in the intensive care unit [1]. Recent studies showed that mRNAs for factors such as IL-10, IGF-1R, HGF, DNA-directed RNA polymerases I, II, and III subunit RPABC1, and VEGF could be loaded into EVs and transported to the target cells to exert translational effects, including anti-inflammation, anti-fibrosis, and anti-apoptosis effects, promoting proliferation, improving renal function, and reducing kidney injury [43, 71]. Reproducible large-scale isolation of exosomes from adipose tissue-derived mesenchymal stem/stromal cells and their application in acute kidney injury Three-dimensional culture of MSCs produces exosomes with improved yield and enhanced therapeutic efficacy for cisplatin-induced acute kidney injury Reversing acute kidney injury using pulsed focused ultrasound and MSC therapy: a role for HSP-mediated PI3K/AKT signaling. MSC-EVs still face numerous challenges and limitations before they can be clinically applied in patients

LIMITATIONS AND FUTURE

Findings

CONCLUSION